Data Snapshot Research Articles

Expanded Access Program (EAP) for Lenalidomide (Revlimid®) Plus Dexamethasone in over 1400 Subjects with Relapsed or Refractory Multiple Myeloma.

Background: Lenalidomide (Revlimid®) in combination with dexamethasone was approved in the US on June 29, 2006 for the treatment of subjects with multiple myeloma who had received at least one prior therapy. On February 28, 2005 based upon a positive interim analysis of two pivotal placebo-controlled Phase III studies, an independent Data Safety Monitoring Board recommended the studies be unblinded and all subjects in both studies be given access to lenalidomide. In April 2005, the FDA in association with myeloma patient advocacy groups requested Celgene establish an expanded access program to make lenalidomide plus dexamethasone available to subjects with relapsed or refractory multiple myeloma while the treatment was awaiting approval.Aim: To provide lenalidomide to multiple myeloma subjects with a high likelihood of benefit and to obtain additional safety data.Methods: Subjects with relapsed or refractory multiple myeloma that received at least 1 prior therapy were eligible. Subjects received 25 mg lenalidomide plus high-dose dexamethasone in 4-week cycles until disease progression was documented, study drug was discontinued, or lenalidomide became commercially available for this indication.Results: Between September 8, 2005 and July 25, 2006, approximately 1400 subjects in the US and Canada were enrolled into the study. A data snapshot taken March 17, 2006 demonstrated that 746 subjects had been enrolled, median age was 63 years, 60% were male, and 66.5% had Stage III disease. Median time on study was 7.1 weeks (0.1–24.4) and median daily dose was 20.5 mg. At least one Grade 3 or 4 adverse event was reported in 261 (35%) of the 746 subjects. Most commonly reported Grade 3–4 events were neutropenia (7.9% of subjects), thrombocytopenia (6.0%), fatigue (3.6%), anemia (3.5%), pneumonia (3.1%) and hyperglycemia (2.0%). These most commonly reported Grade 3–4 adverse events were the same as those found in the previous pivotal studies, however, their frequencies of occurrence were lower in the current study probably due to ongoing data collection and differences in study maturity. Likewise, the most commonly reported adverse events (all grades) were the same as those reported in the two previous pivotal studies.Conclusion: Preliminary data from this expanded access program in over 1400 subjects with multiple myeloma are consistent with results from two earlier Phase III pivotal studies. The EAP of lenalidomide plus dexamethasone in multiple myeloma represents a model of how government, advocacy groups, healthcare providers and industry can work together to quickly provide treatment to subjects in need while a clearly active treatment regimen is awaiting approval.

Vehicle Routing and Staffing for Sedan Service

We present the optimization component of a decision support system developed for a sedan service provider. The system assists supervisors and dispatchers in scheduling driver shifts and routing the fleet throughout the day to satisfy customer demands within tight time windows. We periodically take a snapshot of the dynamic data and formulate an integer program, which we solve to near optimality using column generation. Although the data snapshot is stale by the time a solution is computed, we are able to solve the integer program quickly enough that the solution can be adopted after minor modifications are made by a fast local-search heuristic. The system described in this paper is currently in use and has improved the provider’s productivity significantly.

Mainlobe Jammer Nulling via TSI Finders: A Space Fast-Time Adaptive Processor

An algorithm based on a space fast-time adaptive processor is presented for nulling the mainlobe jammer when the jammer and the target of interest share the same bearing. The computational load involved in the conventional processor, which blindly looks for the terrain-scattered interference (TSI), is required to stack a large number of consecutive range cell returns to form the space fast-time data snapshot making it almost impossible to implement in real time. This issue is resolved via the introduction of a preprocessor (a TSI finder which detects the presence of the minute levels of multipath components of the mainlobe jammer and associated time delays) which directs the STAP processor to select only two desired range returns in order to form the space fast-time data snapshot. The end result is a computationally extremely fast processor. Also a new space fast-time adaptive processor based on the super-resolution approach (eigenvector-based) is presented.

Model-based and data-based processing of moving sources in a shallow water channel

Adaptive MFP algorithms are applied to passively detect and localize a moving source while mitigating interference from surface shipping. A model-based motion compensation algorithm is applied to prevent smearing loss from target motion and extend the observation interval for adaptation. Moving interference is removed by applying a time-varying spatial filter at each data snapshot. The time-variation of the filter decreases the size of the instantaneous interference subspace and allows for a larger signal subspace. The interference subspace is formed by one of three methods. In the first method, knowledge of the ship position is combined with a propagation model to predict the time-varying acoustic interference. A sector null is formed to protect against mismatch degradation. In the second method, a data decomposition is used to determine the strong interferers. The third method combines model-based and data-based approaches. For each method, interference rejection is quantified by presenting SINR values for the candidate algorithm and comparing to conventional approaches. The results use data obtained from the Santa Barbara Channel Experiment. [This work was sponsored by DARPA under Air Force Contract F19628-95-C00022E. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the United States Air Force.]

Assessing the relative detection performance of matched-field processing and conventional beamforming

The primary advantage of matched-field processing (MFP) over conventional plane-wave beamforming is the ability to localize an acoustic source in a single data snapshot; for example, MFP can help to decide whether or not the source is submerged. It is to be expected that MFP will also provide improved detection performance over the plane-wave beamformer when the acoustic pressure field at the array exhibits the complicated behavior that is typically observed in the oceanic waveguide. Accurately quantifying the performance gain is difficult, owing to analytical problems in determining the exact performance of a detector that thresholds many correlated search cells. However, on the basis of simple statistical arguments concerning the effective dimensionality of the search spaces, it is claimed that a rough comparison of detector performance is provided by the ratio of the quadratic forms that are used as the decision variables. This ratio is computed for several array and ocean scenarios, including both a vertical line array in shallow water and a horizontal line array in deep water. Two-dimensional plots (depth and range) are used to illustrate the detection gain that can be provided by matched-field processing.

Operation of the dual magnetometer on Cassini: science performance

As part of the science preparation for the Cassini dual-technique magnetometer experiment, the operational behaviour of the instrument has been considered in terms of the investigation achieving its science aims. The experimental performance falls into two categories: passive, accurate determination of the in situ vector field at Saturn, using nominal mode time series measurements, and event capture, using the data snapshot memory capabilities of the instrument electronics. There are specific science planning aspects during the extended tour of the Saturnian System, for both the magnetospheric coverage in general and for the operational schedule of the instrument. The key science aim of mapping global magnetic structure, for instance, has specific implications for operating the dual mode experiment which differ in each magnetospheric region. The optimal, in situ determination of the intrinsic, planetary magnetic field, in particular, can be achieved through operation of the scalar mode of the Vector Helium magnetometer in addition to the vector measurements taken by the Fluxgate magnetometer. This instrument mode is used in combination with close perigee passes in order to provide high field measurements. During Saturn Orbit Insertion, the start of the Saturnian tour, an extremely low perigee pass is achieved, providing a critical opportunity for measurement. Because the scalar measurement has a restricted field of view, there are also orientation implications for the spacecraft if good science performance is to be realised. A vital opportunity to assess the use of data obtained during scalar operation is provided by the Earth flyby, which can provide high field measurements in a known environment. We relate here the study of these operational issues, based on the expected character of the measured field and in the context of the operating modes of the instrument.

A method for nonasymptotic performance analyses of array signal processing algorithms

This work features a stochastic perturbation theoretic approach that can be used to calculate the performance analyses of array signal processing algorithms for the nonasymptotically large, moderate data regimes that are appropriate for many practical system applications. As an example, the perturbation method is used to develop the expressions for the moments of the MUSIC null spectrum at moderate SNR for independent data snapshot numbers as low as /spl sim/5. Theoretical predictions are shown to be in good agreement with empirical statistical simulation results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>